DNAH9 p.Asp1123Glu

Variant names:

• chr17-11679772-T-A
• rs8071438
• NM_001372.4:c.3369T>A
• DNAH9 p.Asp1123Glu

Your query was ambiguous. Multiple possible variants found:

• chr17-11679772-T-A
• chr17-11679772-T-G

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-1 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -1 classification points (ACMG Germline Pathogenicity v2019). PM2_SupportingBP4_Moderate

The NM_001372.4(DNAH9):c.3369T>A (p.Asp1123Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000131 (AC=2) in the gnomAD database across 152,160 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.000207. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.D1123= (synonymous): Benign (ClinVar VariationId 402776, 2 stars)

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH9 NM_001372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 16 publications found

Genes affected

DNAH9 (HGNC:2953): (dynein axonemal heavy chain 9) This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

DNAH9 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 40

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -1 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Rare in gnomAD for AD/XL gene (popmax AF below threshold) — PM2 Supporting; GnomAD popmax AF = 0.000207 — borderline rare for AD+AR gene (base 0.0001, raised to 0.0005 by highest known P/LP ClinVar AF 0.000629) — PM2 supporting.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001372.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	DNAH9 NM_001372.4	MANE Select	c.3369T>A p.Asp1123Glu	missense	Exon 18 of 69	Prot: NP_001363.2 UniProt:

DNAH9 NM_001372.4

MANE Select

HGVSc / HGVSpc.3369T>Ap.Asp1123Glu

Exon rankExon 18 of 69

missense

Prot: NP_001363.2UniProt: Q9NYC9-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	DNAH9 ENST00000262442.9	TSL:1MANE Select	c.3369T>A p.Asp1123Glu	missense	Exon 18 of 69	Prot: ENSP00000262442.3 UniProt:
	DNAH9 ENST00000454412.6	TSL:5	c.3369T>A p.Asp1123Glu	missense	Exon 18 of 68	Prot: ENSP00000414874.2 UniProt:

DNAH9 ENST00000262442.9

TSL:1MANE Select

HGVSc / HGVSpc.3369T>Ap.Asp1123Glu

Exon rankExon 18 of 69

missense

Prot: ENSP00000262442.3UniProt: Q9NYC9-1

DNAH9 ENST00000454412.6

TSL:5

HGVSc / HGVSpc.3369T>Ap.Asp1123Glu

Exon rankExon 18 of 68

missense

Prot: ENSP00000414874.2UniProt: E7EP17

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.0000131	AC:2	Hom:0	AN:152160	Cov:32
GnomAD2 exomes	AF: 0.00000398	AC:1	Hom:	AN:251422	Cov:
GnomAD4 exome Warning	AF: 6.84e-7	AC:1	Hom:0	AN:1461506	Cov:40
GnomAD4 genome	AF: 0.0000131	AC:2	Hom:0	AN:152160	Cov:32
TOPMed (Bravo) Warning	AF: 0.240	AC:63447	Hom:137	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:108567	AN:226866	Cov:

Showing 6 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.00	0	78346	0.00000719	1	139108

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.1
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.21
DANN	Benign	0.17
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.13	N
FuncVEP CTI	Benign	0.0011
GPN-Star LLR	N/A	8.3
GPN-Star score	N/A	3.8
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.99	T
Mutation Taster	N/A	94/6	polymorphism
MutationAssessor	Benign	-1.8	N
PhyloP100	Benign	0.28
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.039
Sift	Benign	1.0	T
Varity_R	N/A	0.030
VESM-3B	Benign	-3.7

Showing 26 of 26 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs8071438;

hg19: chr17-11583089;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar